Necrotizing enterocolitis (NEC), intestinal perforation (IP) and sepsis are three life-threatening gastrointestinal diseases among neonates and together constitute a leading cause of overall morbidity and mortality in premature newborns. However, there is considerable overlap in the early clinical presentation of NEC, IP and sepsis in newborns. Furthermore, while half of NEC-affected infants will recover with medical therapy alone (the M-class), 30-50% develop a progressive form of the disease (Progressive Necrotizing Enterocolitis) that requires surgery (the S-class) to prevent mortality. Currently utilized clinical parameters including laboratory tests and diagnostic imaging fail to capture the nuanced differences between these entities during their onset and progression. Protein biomarkers detectable in clinically available specimens would provide the needed molecular diagnostic and prognostic “fingerprint” against which we can begin to measure various interventions. Such biomarkers could be used to improved methods for diagnostic and prognostic class prediction in NEC, IP and sepsis, and to improve predictions on responsiveness to known and new therapies. The present invention addresses these issues.
Publications
U.S. Application No. 2009/0191551 teaches using the level of secretor antigens in a biological fluid as a marker to predict the risk of developing NEC. Thuijls G, et al. (2010) Non-invasive markers for early diagnosis and determination of the severity of necrotizing enterocolitis. Ann Surg. 251(6):1174-80, discusses using I-FABP and claudin-3 protein levels in urine and calprotectin protein levels in fecal matter as diagnostic markers of NEC, and I-FABP protein levels in urine as a prognostic marker of disease severity. Evennett N, et al. (2009) A systematic review of serologic tests in the diagnosis of necrotizing enterocolitis. J Pediatr Surg. 44(11):2192-201 is a review of publications that were deemed by the authors to be potentially relevant to diagnostic performance of serological tests in NEC. Young C, et al. (2009) Biomarkers for infants at risk for necrotizing enterocolitis: clues to prevention? Pediatr Res. 65(5 Pt 2):91R-97R is a review that discusses the potential value of genomic and proteomic studies of NEC in the identification of biomarkers for early diagnosis and targeted prevention of this disease.